Planta Med 2014; 80 - WS14
DOI: 10.1055/s-0034-1394555

An eudesmane sesquiterpene from Pluchea odorata (L.) Cass. exhibiting multifaceted anti-neoplastic effects

M Blaschke 1, 3, R McKinnon 1, M Zehl 1, E Urban 2, CN Huu 3, I Zupkó 4, AG Atanasov 1, VM Dirsch 1, G Krupitza 3, B Kopp 1
  • 1Department of Pharmacognosy, University of Vienna, Althanstraße 14, 1090 Vienna, Austria
  • 2Department of Pharmaceutical Chemistry, University of Vienna, Althanstraße 14, 1090 Vienna, Austria
  • 3Institute of Clinical Pathology, Medical University of Vienna, Währinger Gürtel 18 – 20, 1090 Vienna, Austria
  • 4Department of Pharmacodynamics and Biopharmacy, University of Szeged, Eötvös u. 6, H-6720 Szeged, Hungary

Pluchea odorata (L.) Cass. (Asteracea) is used by Maya healers to treat inflammation-associated disorders [1]. Previous studies exhibited the anti-neoplastic effects of its dichloromethane extract (DME) [2, 3]. We show that 30 mg/kg DME significantly inhibited inflammation in a carrageenan-induced rats paw edema model and at similar concentrations (20 µg/mL) DME attenuated TNFα-mediated NF-κβ transactivation in a luciferase-reporter assay using HEK 293 cells. As inflammatory pathways (i.e. NF-κβ) and carcinogenesis are tightly linked, we aimed to isolate anti-proliferative compounds from the DME. Main compounds from the most active fraction were isolated via column and high-performance countercurrent chromatography and their structures were elucidated by NMR spectroscopy and mass spectrometry. One structurally new eudesmane sesquiterpene, (1S,2R,4aR,8aR)-[1-hydroxy-decahydro-1,4a-dimethyl-7-(1-methylethenyl)-6-oxo-2-naphthalenyl]-2,3-dimethyl-oxiranecarboxylic acid ester (a) and four known eudesmanes were obtained: (1S,2R,4aR,8aR)-[1-(acetyloxy)-1,2,3,4,4a,5,6,8a-octahydro-7-(1-hydroxy-1-methylethyl)-1,4a-dimethyl-6-oxo-2-naphthalenyl]-2,3-dimethyl-oxiranecarboxylic acid ester (b), 1-desacetyl-(b) (c), 3-O-angeloyl plucheinol (d), cuauthemone (e). Compound (b) showed a strong proliferation inhibiting (IC50 = 8.9µM after 72h) and pro-apoptotic effect in HL-60 promyelocytic leukemia cells, which was determined by WST-1 assay and Höechst/propidium iodide-staining, respectively. Apoptosis correlated with caspase3 activation and growth inhibition with Cdc25A down-regulation and concomitant G2-M arrest. In addition, 25µM of (b) significantly reduced intravasation of MCF-7 breast cancer cell spheroids through T1S1 lymphendothelial cell (LEC) barriers as determined by CCID-assay. In conclusion, the present work identified a main compound of the ethno-pharmacologically used plant P. odorata with anti-proliferative, anti-metastatic and pro-apoptotic activities.

References:

[1] King-Jones S (2001). Revision of Pluchea Cass. (Compositae, Plucheeae) in the old world. Englera Vol. 23: 3 – 136.

[2] Bauer S, Singhuber J, Seelinger M, Unger C, Viola K, Vonach C, Giessrigl B, Madlener S, Stark N, Wallnofer B, Wagner KH, Fritzer-Szekeres M, Szekeres T, Diaz R, Tut F, Frisch R, Feistel B, Kopp B, Krupitza G, Popescu R (2011). Separation of anti-neoplastic activities by fractionation of a Pluchea odorata extract. Frontiers in Bioscience (Elite edition) 3: 1326 – 1336.

[3] Seelinger M, Popescu R, Seephonkai P, Singhuber J, Giessrigl B, Unger C, Bauer S, Wagner KH, Fritzer-Szekeres M, Szekeres T, Diaz R, Tut FM, Frisch R, Feistel B, Kopp B, Krupitza G (2012). Fractionation of an extract of Pluchea odorata separates a property indicative for the induction of cell plasticity from one that inhibits a neoplastic phenotype. Evidence-based Complementary and Alternative Medicine vol. 2012, Article ID 701927, doi:10.1155/2012/701927 2012.